TREX2

{{Short description|Protein-coding gene in the species Homo sapiens}}

Three prime repair exonuclease 2 is an enzyme that in humans is encoded by the TREX2 gene.{{cite journal | vauthors = Mazur DJ, Perrino FW | title = Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases | journal = J Biol Chem | volume = 274 | issue = 28 | pages = 19655–60 |date=Aug 1999 | pmid = 10391904 | doi =10.1074/jbc.274.28.19655 | doi-access = free }}{{cite web | title = Entrez Gene: TREX2 three prime repair exonuclease 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11219}}

This gene encodes a protein with 3' exonuclease activity. Enzymes with this activity are involved in DNA replication, repair, and recombination. Similarity to an E. coli protein suggests that this enzyme may be a subunit of DNA polymerase III, which does not have intrinsic exonuclease activity.

Newer research has determined that TREX2 is also involved in flap endonuclease activity, as detected in the context of inhibiting gene-editing nickases that generate an extension flap such as prime editors that do not usually create a double-stranded break. This function was first demonstrated in a thesis by Lung in 2021,{{Cite web |last=Lung |first=Genesis |date=Nov 2021 |title=Precise Correction of A1AT E342K by Modified NGA PAM Prime Editing and Determination of Prime Editing Inhibition by TREX2 |url=https://dash.harvard.edu/handle/1/37370046}} and replicated by Koeppel et al. in 2023.{{Cite journal |last=Koeppel |first=Jonas |last2=Weller |first2=Juliane |last3=Peets |first3=Elin Madli |last4=Pallaseni |first4=Ananth |last5=Kuzmin |first5=Ivan |last6=Raudvere |first6=Uku |last7=Peterson |first7=Hedi |last8=Liberante |first8=Fabio Giuseppe |last9=Parts |first9=Leopold |date=2023 |title=Prediction of prime editing insertion efficiencies using sequence features and DNA repair determinants |url=https://www.nature.com/articles/s41587-023-01678-y |journal=Nature Biotechnology |volume=41 |pages=1444-1456}} Subsequently, TREX2 has become incorporated into fusion enzymes for genetic engineering by multiple research groups for the purposes of reducing off-target edits which include chromosomal translocations and mismatched insertions.{{Cite journal |last=Yin |first=Jianhang |last2=Lu |first2=Rusen |last3=Xin |first3=Changchang |last4=Wang |first4=Yuhong |last5=Ling |first5=Xinyu |last6=Li |first6=Dong |last7=Zhang |first7=Weiwei |last8=Liu |first8=Mengzhu |last9=Xie |first9=Wutao |last10=Kong |first10=Lingyun |last11=Si |first11=Wen |last12=Wei |first12=Ping |last13=Xiao |first13=Bingbing |last14=Lee |first14=Hsiang-Ying |last15=Liu |first15=Tao |date=Mar 2022 |title=Cas9 exo-endonuclease eliminates chromosomal translocations during genome editing |url=https://www.nature.com/articles/s41467-022-28900-w |journal=Nature Communications |volume=13 |pages=1204}}{{Cite journal |last=Wang |first=Yue |last2=Feng |first2=Yi-Li |last3=Liu |first3=Qian |last4=Liu |first4=Si-Cheng |last5=Huang |first5=Zhi-Cheng |date=Dec 2023 |title=TREX2 enables efficient genome disruption mediated by paired CRISPR-Cas9 nickases that generate 3′-overhanging ends |url=https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(23)00290-1 |journal=Cell Molecular Therapy |volume=34 |issue=102072}}

Mutations in this gene may lead to Aicardi-Goutieres syndrome.

References

{{cite journal | vauthors=Shevelev IV, Hübscher U |title=The 3' 5' exonucleases |journal=Nat. Rev. Mol. Cell Biol. |volume=3 |issue= 5 |pages= 364–76 |year= 2002 |pmid= 11988770 |doi= 10.1038/nrm804 |s2cid=31605786 }}
{{cite journal |vauthors=Esposito T, Ciccodicola A, Flagiello L, etal |title=Expressed STSs and transcription of human Xq28 |journal=Gene |volume=187 |issue= 2 |pages= 185–91 |year= 1997 |pmid= 9099879 |doi=10.1016/S0378-1119(96)00772-X }}
{{cite journal | vauthors=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=10.1101/gr.143000 | pmc=310948 }}
{{cite journal |vauthors=Li T, Duan W, Yang H, etal |title=Identification of two proteins, S14 and UIP1, that interact with UCH37 |journal=FEBS Lett. |volume=488 |issue= 3 |pages= 201–5 |year= 2001 |pmid= 11163772 |doi=10.1016/S0014-5793(00)02436-4 |bibcode=2001FEBSL.488..201L |hdl=10536/DRO/DU:30009147 |s2cid=40717095 |hdl-access=free }}
{{cite journal |vauthors=Simpson JC, Wellenreuther R, Poustka A, etal |title=Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing |journal=EMBO Rep. |volume=1 |issue= 3 |pages= 287–92 |year= 2001 |pmid= 11256614 |doi= 10.1093/embo-reports/kvd058 | pmc=1083732 }}
{{cite journal | vauthors=Mazur DJ, Perrino FW |title=Structure and expression of the TREX1 and TREX2 3' --> 5' exonuclease genes |journal=J. Biol. Chem. |volume=276 |issue= 18 |pages= 14718–27 |year= 2001 |pmid= 11278605 |doi= 10.1074/jbc.M010051200 |doi-access= free }}
{{cite journal | vauthors=Mazur DJ, Perrino FW |title=Excision of 3' termini by the Trex1 and TREX2 3'-->5' exonucleases. Characterization of the recombinant proteins |journal=J. Biol. Chem. |volume=276 |issue= 20 |pages= 17022–9 |year= 2001 |pmid= 11279105 |doi= 10.1074/jbc.M100623200 |doi-access= free }}
{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
{{cite journal | vauthors=Shevelev IV, Beliakova NV, Kravetskaia TP, Krutiakov VM |title=[The correcting role of autonomous 3'-->5' exonucleases in mammalian multienzyme DNA polymerase complexes] |journal=Mol. Biol. (Mosk.) |volume=36 |issue= 6 |pages= 1055–61 |year= 2003 |pmid= 12500544 }}
{{cite journal | vauthors=Shevelev IV, Ramadan K, Hübscher U |title=The TREX2 3'-->5' exonuclease physically interacts with DNA polymerase delta and increases its accuracy |journal=ScientificWorldJournal |volume=2 |pages= 275–81 |year= 2004 |pmid= 12806015 |pmc=6009725 |doi= 10.1100/tsw.2002.99 |doi-access=free }}
{{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
{{cite journal |vauthors=Wiemann S, Arlt D, Huber W, etal |title=From ORFeome to biology: a functional genomics pipeline |journal=Genome Res. |volume=14 |issue= 10B |pages= 2136–44 |year= 2004 |pmid= 15489336 |doi= 10.1101/gr.2576704 | pmc=528930 }}
{{cite journal |vauthors=Perrino FW, Krol A, Harvey S, etal |title=Sequence variants in the 3'-->5' deoxyribonuclease TREX2: identification in a genetic screen and effects on catalysis by the recombinant proteins |journal=Adv. Enzyme Regul. |volume=44 |pages= 37–49 |year= 2005 |pmid= 15581481 |doi= 10.1016/j.advenzreg.2003.11.010 }}
{{cite journal | vauthors=Perrino FW, Harvey S, McMillin S, Hollis T |title=The human TREX2 3' -> 5'-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis |journal=J. Biol. Chem. |volume=280 |issue= 15 |pages= 15212–8 |year= 2005 |pmid= 15661738 |doi= 10.1074/jbc.M500108200 |doi-access= free }}
{{cite journal |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026 }}
{{cite journal |vauthors=Mehrle A, Rosenfelder H, Schupp I, etal |title=The LIFEdb database in 2006 |journal=Nucleic Acids Res. |volume=34 |issue= Database issue |pages= D415–8 |year= 2006 |pmid= 16381901 |doi= 10.1093/nar/gkj139 | pmc=1347501 }}
{{cite journal | vauthors=Hahn Y, Lee B |title=Human-specific nonsense mutations identified by genome sequence comparisons |journal=Hum. Genet. |volume=119 |issue= 1–2 |pages= 169–78 |year= 2007 |pmid= 16395595 |doi= 10.1007/s00439-005-0125-6 |s2cid=21059468 |url=https://zenodo.org/record/1232721 }}
{{cite journal | vauthors=Chen MJ, Ma SM, Dumitrache LC, Hasty P |title=Biochemical and cellular characteristics of the 3' -> 5' exonuclease TREX2 |journal=Nucleic Acids Res. |volume=35 |issue= 8 |pages= 2682–94 |year= 2007 |pmid= 17426129 |doi= 10.1093/nar/gkm151 | pmc=1885668 }}
{{cite journal | vauthors=Parra D, Manils J, Castellana B, Viña-Vilaseca A, Morán-Salvador E, Vázquez-Villoldo N, Tarancón G, Borràs M, Sancho S, Benito C, Ortega S, and Soler C |title=Increased Susceptibility to Skin Carcinogenesis in TREX2 Knockout Mice|journal=Cancer Research |volume=69 |issue= 16 |pages= 6676–84|year= 2009 |pmid= 19654293 |doi= 10.1158/0008-5472.CAN-09-1208 |doi-access= free }}

External links

{{PDBe-KB2|Q9BQ50|Human Three prime repair exonuclease 2}}
{{PDBe-KB2|Q9R1A9|Mouse Three prime repair exonuclease 2}}

TREX2

References

Further reading

External links